Maltol (3-hydroxy-2-methyl-4-pyrone), is a naturally occurring, non-toxic compound and common food additive. Many biologically important metals form stable complexes with maltol. Its stability arises from the easiness to deprotonate and to behave as an anionic, bidentate metal chelator. There are numerous metal-maltol complexes used in biomedical application. For instance, iron(III)-maltol complex has been used in the treatment of anemia and tris(maltolato)aluminum complex has found applications in the Alzheimer disease. Perhaps the most significant is bis(maltolato)oxovanadium(IV), which has been the subject of many chemical and physiological studies due to its potent insulinomimetic properties. This complex is an excellent glucose- and lipid-lowering insulin mimetics and it is currently evaluated in clinical trials.
Titanium(IV) complexes are widely used for a variety of purposes, mainly as catalysts in a diversity of organic reactions. But titanium(IV) complexes also have a role in the bioinorganic chemistry with two classical examples: titanocene dichloride (Cp2TiCl2) and budotitane (Ti(bza)2(OEt)2), which exhibit anti-cancer activities. With the discovery of the biological properties of these two Ti(IV) complexes, many research groups have devoted their efforts to synthesize new titanium complexes with enhanced antitumor activity.
Titanocene dichloride and budotitane possess the same limitation, low hydrolytic stability at physiological pH. As a result, the mechanistic aspects and hydrolysis products of these antitumor species remain mostly uncharacterized. The synthesis of hydrolytically stable Ti(IV) complexes at physiological pH (both organometallic and inorganic) with biological properties is still a challenge. Among oxygen containing chelating ligands, maltol has shown to form non-toxic complexes.
Thus, a new Ti(IV)-maltol complex with two reactive OH ligands has been synthesized at low pH. At high pH, this species further reacts to form a tetrameric species. These complexes could have potential for applications in catalysis and in the biomedical field.